Relative Influence of Scaffold Design/Material Parameters On Bone Regeneration

描述（由申请人提供）：骨支架应提供足够的承重并增强组织再生。然而，目前，几乎没有严格的比较信息可以告诉人们，给定的材料与给定的结构设计将提供足够的承重并提供最佳的骨再生。作为一个出发点，我们将承载与有效弹性和强度相关联，并将增强组织再生与渗透性材料作为设计变量。那么基本的问题就变成了“支架是否可以设计成保持最小的承载特性，同时最大限度地提高渗透性，以及相对于材料的骨传导性，骨再生的渗透性有多重要？”“我们假设骨组织工程支架应该由具有最大渗透性的骨传导材料制成，以增强骨再生。此外，支架设计应当使得在时间0时的机械性能可以在人骨小梁的范围内实现50 MPa的模量和2 MPa的抗压强度。与此假设相关，我们试图回答以下问题：1）支架是否可以设计为满足最低50/2 MPa刚度/强度标准，以及这些机械性能的退化如何取决于渗透性和材料？和2）渗透性在骨再生中起重要作用还是材料是压倒性因素？我们将通过三个具体目标来回答这些基本的支架设计问题：具体目标1：计算设计和制造具有最大和次最大渗透性的60%的单一孔隙率的HA/TCP，PLLA和PCL支架架构具体目标2：确定设计支架的弹性模量和极限强度，满足最小人体骨小梁值。确定设计/材料如何影响机械性能退化。具体目标3：通过递送BMP-7转导的人成纤维细胞，确定设计的渗透性和材料对小鼠模型中8周和16周的骨再生的影响。这项研究将为骨组织工程师提供关键信息，以支架渗透性和材料骨组织支架设计的相对重要性，这将是至关重要的临床骨组织工程应用。

DESCRIPTION (provided by applicant): Bone scaffolds should provide adequate load bearing and enhance tissue regeneration. However, at present, there is little rigorous comparative information that will tell one that a given material with a given architecture design will provide adequate load bearing and give the best bone regeneration. As a starting point, we associate load bearing with effective elasticity and strength, and enhanced tissue regeneration with permeability material as design variables. Then the fundamental question becomes "can scaffolds be designed to maintain minimum loading bearing characteristics while maximizing permeability and how important is permeability for bone regeneration relative to material osteoconductivity?" We hypothesize that Bone tissue engineering scaffolds should be fabricated from the most osteoconductive material with maximal permeability to enhance bone regeneration. Furthermore, the scaffold design should be such that the mechanical properties at time 0 can achieve a modulus of 50 MPa and compressive strength of 2 MPa, within the range of human trabecular bone. Related to this hypothesis, we seek to answer the questions: 1) can scaffolds be designed to meet the minimum 50/2 MPa stiffness/strength criteria and how does degradation of these mechanical properties depend on permeability and material?, and 2) does permeability play a significant role in bone regeneration or is material an overwhelming factor? We will answer these fundamental scaffold design questions through three specific aims: Specific Aim 1: Computationally design and fabricate scaffolds architectures from HA/TCP, PLLA, and PCL at a single porosity of 60% with maximal and sub-maximal permeability Specific Aim 2: Determine elastic modulus and ultimate strength of designed scaffolds at 0 meet minimum human trabecular bone values. Determine how design/material influence degradation of mechanical properties. Specific Aim 3: Determine the influence of designed permeability and material on bone regeneration in a mouse model at 8, and 16 weeks by delivering BMP-7 transduced human fibroblasts. This study will give bone tissue engineers critical information as to as to the relative importance of scaffold permeability and material bone tissue scaffold design, which will be crucial for clinical bone tissue engineering applications.